A wound or may be accidental, the result of surgical intervention or the effect of a disease or genetic condition. The ideal end result of wound healing is restoration of tissues morphology. One important part of the wound healing process is to form connective tissues or scar tissue that may support the healing tissues during wound healing and regeneration. However, in many cases during wound healing, the newly formed connective tissues (scar tissue) may interfere negatively with the normal function of the tissue intended to be healed.
Wound healing, with the formation of connective tissues may also induce adhesions that may induce pathological conditions. For example, scar tissue may induce cosmetically undesirable results such as cheloid formation. Examples of adhesions and scarring may be found virtually in any organ or tissue undergoing wound healing after trauma or surgery. Following abdominal surgery and following gynecological surgery it is not uncommon that the surgical procedure may induce adhesions that may both make later surgery more difficult and even induce pathological conditions such as ileus.
In spinal surgery it is common to have a situation with a dense scar formation called epidural fibrosis. This may in certain cases induce significant difficulties for repeated surgery and can induce compression of the adjacent nerve tissue. In other organs excessive wound healing may induce unwanted fixation of tissues and structures that may reduce function and induce pathological conditions.
Intercellular adhesion mediated by VLA-4 and other cell surface receptors is associated with a number of inflammatory responses. At the site of an injury or other inflammatory stimulus, activated vascular endothelial cells express molecules that are adhesive for leukocytes. The mechanics of leukocyte adhesion to endothelial cells involves, in part, the recognition and binding of cell surface receptors on leukocytes to the corresponding cell surface molecules on endothelial cells. Once bound, the leukocytes migrate across the blood vessel wall to enter the injured site and release chemical mediators to combat infection.
In intra-organ systems, tissue damage occurs that elicits an adhesion mechanism that results in migration or activation of leukocytes that can be damaging. For example, the initial insult following myocardial ischemia to heart tissue is complicated by leukocyte entry to the injured tissue causing still further insult. Inflammatory conditions mediated by adhesion mechanisms are almost always deleterious, for example, asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), multiple sclerosis, rheumatoid arthritis, tissue transplantation, tumor metastasis, meningitis, encephalitis, stroke, and other cerebral traumas, nephritis, retinitis, atopic dermatitis, psoriasis, myocardial ischemia and acute leukocyte-mediated lung injury such as that which occurs in adult respiratory distress syndrome.
Hydrogels have the potential to be useful in healing. However, one difficulty associated with in situ hydrogel forming compositions is that certain compositions may worsen tissue inflammation at the site of administration. A possible explanation for this effect is that highly reactive composition components that are capable of rapid gel formation may adversely affect tissue surfaces.
Therefore, it would be useful to develop a hydrogel which combines a barrier aspect with a biofunctional aspect which affects cellular adhesion and prevents clinically adverse tissue adhesions.